title: The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.
abstract: Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using μ-calpain knockout (KO) mice in comparison with control wild-type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up regulation of other proteolytic systems. The KO mice showed significantly greater m-calpain protein abundance (P < 0.01) and activity (P < 0.001), and greater caspase 3/7 activity (P < 0.05). At 30 wk of age, KO mice showed increased protein:DNA (P < 0.05) and RNA:DNA ratios (P < 0.01), greater protein content (P < 0.01) at the expense of lipid deposition (P < 0.05), and an increase in size and number of fast-twitch glycolytic muscle fibers (P < 0.05), suggesting that KO mice exhibit an increased capacity to accumulate and maintain protein in their skeletal muscle. Also, expression of proteins associated with muscle regeneration (neural cell adhesion molecule and myoD) were both reduced in the mature KO mice (P < 0.05 and P < 0.01, respectively), indicating less muscle regeneration and, therefore, less muscle damage. These findings indicate the concerted action of proteolytic systems to ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain system's involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass.
authors.affiliation: USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Kemp
authors.forename: W T
authors.initials: WT
authors.lastname: Oliver
authors.forename: T L
authors.initials: TL
authors.lastname: Wheeler
authors.forename: A H
authors.initials: AH
authors.lastname: Chishti
authors.forename: M
authors.initials: M
authors.lastname: Koohmaraie
mesh_terms: D000818:Animals; D002154:Calpain / Q000235:genetics* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D020868:Gene Silencing; D051379:Mice; D018345:Mice, Knockout; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D059748:Proteolysis
chemical_list: D009124:Muscle Proteins; D002154:Calpain; C449002:mu-calpain; C112682:Capn1 protein, mouse